The long-term goal of this research is to understand how the olfactory system encodes odor information, and how olfactory sensory codes are transformed sequentially through different processing stages along the central projection pathways. Olfactory coding and processing have been extensively studied with two major approaches: (1) electrophysiology of single neurons, which can record neural activity at any tissue depth, but blindly without knowing network context in reference to upstream coding patterns;and (2) CCD camera imaging of spatiotemporal pattern of activated glomeruli, which is ideal for revealing the initial glomerulus-based codes, but lacks single-cell resolution and deep penetration required for exploring odor codes beyond the glomerular layer. This grant is aimed at bridging such a gap between single-cell physiology and large-scale CCD camera imaging, so as to unify the two large datasets already available in the literature. First, using a new transgenic mouse model, we will provide a direct comparison between the pre- and postsynaptic odor maps within the glomerular layer, and test the hypothesis that lateral circuits intrinsic to this layer can support interglomerular lateral inhibition and/or excitation for initial odor-map transformation. Second, by combining in vivo two-photon calcium imaging and targeted single-glomerulus dye labeling, we will perform a systematic analysis of odor ensemble codes carried by the mitral/tufted cells associated with a common glomerulus. We will test the hypothesis that both the overall size and distribution pattern of a glomerulus-defined active cell ensemble can be effective coding factors for odor intensity at least and maybe also identity. Finally, by imaging the mitral cell population with diverse glomerular projections, we will analyze the cross-glomerular odor ensemble responses in the context of corresponding glomerular activation patterns. We will study how the glomerulus-based odor codes break down into distributed mitral-cell population codes, and ask what is the benefit of redistributing odor signals which have just converged via the nose-to-bulb projection. Collectively, these studies should not only have a significant impact on our understanding of the neural basis of odor processing and discrimination, but could also yield novel and more general principles on how the brain transforms neural codes for achieving sensory and perceptive functions. PUBLIC HEALTH RELEVANCE The sense of smell plays an important role in our daily life style involving flavor and fragrance appreciation. Dysfunction of the olfactory system happens in many human diseases such as eating-related obesity and early development of Alzheimer's disease. The general goal of this grant in understanding the neural basis of odor coding and processing will not only help the diagnosis and treatment of these diseases, but will also promote people's life quality in general.